Clinical significance of abdominal scintigraphy using 99mTc-HMPAO-labelled leucocytes in patients with seronegative spondyloarthropathies

Abdominal scintigraphy shows silent gut inflammation in patients with spondyloarthropathies (Sp) without clinical evidence of gut inflammation. Abdominal scintigraphy images are different than those obtained in patients with ulcerative colitis or Crohn's disease and are not related to the anti-inflammatory drugs administered. The aim of this study was to examine the clinical associations of findings on abdominal scintigraphy in patients with Sp. A total of 204 Sp patients (European Spondylarthropathy Study Group 1991 criteria) and 54 non-Sp controls receiving non-steroidal anti-inflammatory drugs were studied. Abdominal scintigraphy images were obtained at 30 and 120 min after injection of technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO)-labelled leucocytes. ^99mTc-HMPAO-labelled leucocyte scans were positive in 104 Sp patients (50.9%) and in six non-Sp controls (2.9%) (P<0.001; OR=8.32; 95% CI=3.23-22.67). Silent gut inflammation was not associated with any of the following: age of onset, duration of evolution, sex, family history of Sp or psoriasis, articular manifestations, extra-articular manifestations, radiological findings or HLA-B27 positivity. Positive abdominal scintigraphy was associated with active disease (P<0.0001; OR=52.7; 95% CI=19-145.6) and an increase in the C-reactive protein (P<0.005; OR=3.4; 95% CI=1.5-7.4). It is concluded that (a) abdominal scintigraphy using ^99mTc-HMPAO-labelled leucocytes is of value in detecting the silent gut inflammation in Sp patients, and (b) silent gut inflammation is related to the clinical activity, but is not associated with any particular type of illness or with HLA-B27.     

Caloric and rotatory chair test results in patients with Ménière's disease.

OBJECTIVES: To determine whether an association exists between the parameters of the caloric and rotatory chair tests in patients with unilateral Ménière's disease. METHODS: Patients with unilateral Ménière's disease (n = 100) were subjected to the caloric and the rotatory chair test (sinusoidal harmonic acceleration and impulsive tests) on the same day. Canal paresis and directional preponderance were assessed in the caloric test, and different variables were measured in the rotatory chair test based on the existence of abnormal parameters in the vestibulo-ocular reflex at two or three consecutive frequencies of those tested and on the time constant of the vestibulo-ocular reflex. STUDY DESIGN AND SETTING: A prospective study was conducted at a University hospital. RESULTS: An abnormal result in the caloric test was obtained from 73% of the patients. In the rotatory chair test, the most frequent abnormal findings involved increases in the normal phase lead at 2 consecutive frequencies tested (23%). There was a stronger association between an abnormal result in phase, gain, and/or symmetry at three adjacent frequencies and a pathological result in the caloric test. CONCLUSION: Very few of the criteria used to define the caloric and rotatory chair tests seem to be associated. This confirms previous knowledge that both tests examine vestibulo-ocular reflex by different ways. Only when vestibular dysfunction is severe enough (manifested by the finding of an abnormal result in at least three consecutive frequencies in the rotatory chair test), the caloric test is also found to be abnormal.     

Expression of BAG-1 and BcL-2 Proteins Before and After Neoadjuvant Chemotherapy of Locally Advanced Breast Cancer

It has been suggested that expression of anti-apoptotic proteins such as Bcl-2 or BAG-1 may confer cellular resistance to chemotherapy. A corollary of this hypothesis is that expression of these proteins may predict clinical response to treatment and that Bcl-2- or BAG-1-positive cells may selectively be enriched in postchemotherapy tissue specimens. The goal of this exploratory pilot study was to assess these two predictions by using immunohistochemistry in 29 paired pre- and postchemotherapy breast tissue specimens obtained from patients who underwent preoperative doxorubicin-based chemotherapy. All breast cancers expressed BAG-1 protein, and, in individual tumors, 40-100% of neoplastic cells stained positive for this protein. Homogenous cytoplasmic staining was typically observed, though neoplastic cells also showed nuclear staining in many specimens. We found no correlation between prechemotherapy expression of BAG-1 and subsequent pathological response to cytotoxic therapy. Paired pre- and posttreatment specimens showed similar levels of BAG-1 expression when residual tumor could be assessed. Bcl-2 was expressed in 55% of cancers and was localized to the cytoplasm. Absence of Bcl-2 expression in prechemotherapy specimens was associated with more frequent complete pathological response (58% vs. 20%; p = 0.04). However, similar to BAG-1, no difference between pre- and posttherapy expression of Bcl-2 was observed in neoplastic cells in paired tissue specimens. These observations suggest that BAG-1 contributes an important cellular function to breast epithelial cells, which is reflected by its ubiquitous expression in these tissues. However, it does not appear to determine response to doxorubicin-based chemotherapy. In contrast, lack of Bcl-2 expression was associated with a higher probability of complete pathological response to doxorubicin-based chemotherapy.     

Stress and hippocampal abnormalities in psychiatric disorders.

The hippocampus plays a main role in regulating stress response in humans, but is itself highly sensitive to neurotoxic effects of repeated stressful episodes. Hippocampal atrophy related to experimental stress has been reported in laboratory studies in animals. Several controlled brain imaging studies have also shown hippocampal abnormalities in psychiatric disorders, including posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and borderline personality disorder (BPD). This paper reviews the physiological role of the hippocampus in stress circuitry and the effects of stress on cognitive functions mediated by the hippocampus. We also review brain imaging studies investigating hippocampus in PTSD, MDD, and BPD. This literature suggests that individuals with PTSD, MDD, and BPD may suffer hippocampal atrophy as a result of stressors associated with these disorders. Prospective, longitudinal studies will be needed in high-risk offspring and first-episode subjects to explore the relationship between stress and hippocampal atrophy in these neuropsychiatric illnesses.     

A multi-centre,randomised, double-blind,placebo-controlled clinical trial of methylphenidate in the initial treatment of acute mania (MEMAP study)

Based on many clinical and preclinical findings the ‘vigilance regulation model of mania’ postulates that an unstable regulation of wakefulness is a pathogenetic factor in both mania and Attention Deficit Hyperactivity Disorder (ADHD) and induces hyperactivity and sensation seeking as an autoregulatory attempt to stabilize wakefulness. Accordingly, stimulant medications with their vigilance stabilizing properties could have rapid antimanic effects similar to their beneficial effects in ADHD. The MEMAP study – a multi-center, double-blind, placebo-controlled and randomized clinical trial (RCT) – assessed the antimanic efficacy and safety of a 2.5-day treatment with methylphenidate (20–40 mg/day). Of 157 screened patients with acute mania, 42 were randomly assigned to receive 20–40 mg per day of methylphenidate in one or two applications, or placebo. The primary outcome was the change in Young Mania Rating Scale (YMRS) sum scores from baseline to day 2.5 in the methylphenidate group compared to the placebo group. A group sequential design was chosen to justify early RCT termination based on efficacy or futility at an interim analysis after inclusion of 40 patients. In the interim analysis, the change from baseline in the YMRS total score at day 2.5 was not significantly different between both groups (F(1,37)=0.23; p=0.64). Thus, futility was declared for methylphenidate and the RCT was stopped. In summary, although methylphenidate was well tolerated and safe in the full analysis set, it failed to show efficacy in the treatment of acute mania. Trial registration: clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number: NCT01541605).     

Mandibulofacial dysostosis, acral anomalies and frontonasal dysplasia: a new form of acrofacial dysostosis

We describe a stillborn female with acrofacial dysostosis and frontonasal dysplasia. She had protrusion of the forehead, with marked hypertelorism and absence of the nose but with the rhinencephalon present. Autopsy showed wide cranial sutures, severe hydrocephalus with separation of the right and left hemispheres of the brain, preservation of the olfactory bulb and first and second cranial nerves. The child also had small kidneys bilaterally, rectal atresia and an absent anus with rectovaginal fistula. These clinical findings suggest a new form of acrofacial dysostosis.     

Development of a job exposure matrix for the epidemiological follow-up of workers in the French nuclear industry

BACKGROUND: A pilot study was carried out in the AREVA NC Pierrelatte nuclear facility in order to investigate a possible carcinogenic effect of internal radiation exposure among nuclear workers in France. The objective of this study was to develop a method for retrospective reconstruction of the occupational exposure to internal radiation from uranium and associated chemical exposures. METHODS: A plant- and period-specific job exposure matrix (JEM) was designed. Job groups and exposure agents groups including uranium compounds and other chemical agents known as being carcinogenic, mutagenic or toxic were defined by an expert committee. Exposure was evaluated by active and retired workers included in the evaluator committee. A quantitative assignment of quantity and frequency of handling (both coded from 0 to 3) was performed for each agent groups using a method derived from the Delphi technique. RESULTS: In all, 23 experts and 353 evaluators participated to the JEM elaboration. A final JEM involved 232 "job-periods" presenting throughout the plant period 1960-2006 and 22 exposure agents groups in use at the plant. Six of them involved uranium compounds classified by their blood-transferability and toxicity characteristics. A first validation of the JEM by experts in radiological protection and industrial hygiene showed an acceptable internal consistency. CONCLUSION: In the context of missing past exposure measurement data, the plant- and period-specific job exposure matrices may be considered as a valid alternative for exposure estimation. This method may be applied to other nuclear plants and offers allowance to investigate a possible carcinogenic effect of internal radiation exposure among nuclear workers.     

Isolation of antihemorrhagic factors in opossum (Didelphis virginiana) serum using a monoclonal antibody immunoadsorbent

The antihemorrhagic factor in opossum (Didelphis virginiana) serum isolated by Sephadex G-200 gel filtration and DEAE A-50 ion exchange chromatography was used as antigen to immunize BALB/c mice. Hybrid cell lines secreting monoclonal antibodies against antihemorrhagic factor were produced by fusion of Sp2/0 myeloma cells with spleen cells of the immunized mice. The ascites fluid was produced in BALB/c mice. The monoclonal antibody in the ascites fluid was partially purified by DEAE A-50 ion exchange and coupled to CNBr-activated isolation of isolation of antihemorrhagic factor. The neutralization capacity of the conventionally isolated antihemorrhagic factor was 14.6 times and the affinity isolated antihemorrhagic factor was 16.8 times that of crude opossum serum. Both antihemorrhagic factors were homogeneous, with one fast migrating band in the area of albumin shown by polyacrylamide gel electrophoresis. However, the antihemorrhagic factor showed one heavy band and one faint band in SDS-polyacrylamide electrophoresis, as well as in isoelectric focusing. The molecular weight of the heavy band was estimated to be 65,000 with a value of p1 4.8 and the faint band was 57,000 with a value of pI 4.1.